Optic Neuropathy in Hodgkin's Disease R. Michael Siatkowski, M.D., Byron L. Lam, M.D., Norman J. Schatz, M.D., Joel S. Glaser, M.D., Sandra F. Byrne, and J. Randall Hughes, B.S.
Hodgkin's disease is a rare cause of infiltrative optic neuropathy, which typically evolves late in the disease course. We managed an unusual case of isolated optic neuropathy in a 21-year-old man occurring during clinical remission from Hodgkin's disease. Radiotherapy and treatment with high-dose systemic corticosteroids resulted in dramatic improvement in vision. Even without other evidence of recurrent disease, acute-onset optic neuropathy in a patient with a history of a lymphoproliferative disorder should raise the question of a reemergence of the malignancy. C E N T R A L NERVOUS SYSTEM involvement in Hodgkin's disease may occur in up to 15% of cases, 1 but optic nerve infiltration is rare. Two histopathologically documented cases have been described. 2 · 3 More recently, a survey at the Massachusetts Eye and Ear Institute and the Massachusetts General Hospital identified without details only three cases over a 25-year period. 4 Hodgkin's disease of the central nervous sys tem may rarely be primary, 6 7 but usually is a result of hematogenous metastasis or direct tumor extension from contiguous structures, for example, the retroperitoneal space or paranasal sinuses. Optic neuropathy occurs typical ly late in the disease course, preceded by other central nervous system or systemic abnormali ties. Our case of infiltrative optic neuropathy in Hodgkin's disease documents that this compli cation may occur as the sole manifestation of disease recurrence in a patient otherwise in clinical remission.
Accepted for publication Aug. 14, 1992. From the Bascom Palmer Eye Institute, Miami, Florida. This study was presented in part at the 24th Annual Frank B. Walsh Meeting, Los Angeles, California, Feb. 28, 1992. Reprint requests to Joel S. Glaser, M.D., 900 N.W. 17th St., Miami, FL 33136.
Case Report A 21-year-old man was initially examined in October 1988 because of complaints of fever, and neck and inguinal masses. Pathologic diag nosis was nodular sclerosis Hodgkin's disease, stage HIB (disease above and below the dia phragm, and systemic symptoms). Twelve cy cles of chemotherapy were prescribed for the patient, but he received only five because of adverse effects (one course of methotrexate, vincristine sulfate, procarbazine, and prednisone; three courses of doxorubicin hydrochloride, bleomycin, vincristine, and dacarbazine; and one course of bleomycin, vincristine, cyclophosphamide, procarbazine, and prednisone). No chemotherapy was received after May 1989 and the patient remained without symptoms for more than two years. On Aug. 11, 1991, the patient was examined at our institution for loss of vision in the left eye two weeks previously, which was associated with severe orbital pain made worse with ocu lar movement. The patient also complained of a mild frontal headache and bilateral paresthesias of the chest that extended down both ante rior axillary lines. Neuro-ophthalmic examination disclosed a visual acuity of 20/20 in the right eye, with a full visual field, and normal anterior segment and fundus. The visual acuity in the left eye was counting fingers, with a large central scotoma and an afferent pupillary defect that measured 3.0 log units. The anterior segment was normal and there was no vitreitis. The left optic disk was diffusely swollen with surrounding hemor rhages (Fig. 1). Ocular motility was normal. B-scan echography showed a normal right optic nerve and a notably enlarged left optic nerve with marked disk elevation (Fig. 2). By standardized A-scan echography, the right op tic nerve measured 3.8 mm with a positive 30-degree test (3.2 mm), which indicated increased subarachnoid fluid around the nerve. 8 The left optic nerve was markedly en-
©AMERICAN JOURNAL OF OPHTHALMOLOGY 114:625-629, NOVEMBER, 1992
625
626
November, 1992
AMERICAN JOURNAL OF OPHTHALMOLOGY
Fig. 1 (Siatkowski and associates). Swollen left optic disk, and peripapillary retinal folds and hemor rhages. larged with low reflectivity. Its diameter was 6.3 mm with a negative 30-degree test (6.4 mm), which suggested solid thickening of the nerve (Fig. 3). (Normal A-scan values of optic nerve diameter range from 2.3 to 3.3 mm. 8 ) Magnetic resonance imaging demonstrated en largement and gadolinium enhancement of the left optic nerve from the globe to the optic canal (Fig. 4). The right optic nerve was normal. Results of a general physical examination were normal, without adenopathy or visceromegaly. Lumbar puncture disclosed an opening pressure of 200 mm H 2 0, a protein concentra tion of 40 mg/dl, a glucose level of 65 m g / d l , and no cells. Cerebrospinal fluid VDRL, cryptococcal antigen, and bacterial and fungal cul tures were negative. Cytology screen, including immunoassay, detected no malignant cells. Fur ther examination included thoracic radiogra phy, computed tomography of the abdomen arid pelvis, and bone marrow biopsy, all of which had normal results. Lymphomatous infiltration of the left optic nerve was strongly suspected, and 2,000 cGy of radiation were delivered over ten daily sessions to the left optic nerve. Intravenous methylprednisolone, 250 mg four times daily, was adminis tered simultaneously for three days, followed by oral prednisone, 60 mg daily, which was tapered over a three-week period. Within one week, the visual acuity in the left
Fig. 2 (Siatkowski and associates). B-scan echograms of left optic nerve. Top, Vertical cross section; arrows indicate enlarged nerve sheath. Bottom, Lon gitudinal section through elevated disk and anterior optic nerve (ON). eye improved to 20/400, with a decrease in the size of the scotoma. A six-week follow-up ex amination on Sept. 25, 1991, disclosed a visual acuity of 20/60 in the left eye. The disk swell ing had resolved, but with a trace of temporal pallor. The left afferent pupillary defect now measured 0.9 log unit. Repeat magnetic reso nance imaging six weeks after treatment showed a left optic nerve of normal size with only minimal gadolinium enhancement (Fig. 4). Eight weeks after the visual symptoms devel oped, a 1.5-cm right anterior cervical lymph node appeared. A biopsy confirmed nodular sclerosis Hodgkin's disease (Fig. 5), and chem otherapy was reinstituted.
Discussion Hodgkin's disease causes a variety of oph thalmic problems, including oculomotor pal sies, proptosis, iritis, retinal arterial and
Vol. 114, No. 5
Hodgkin's Lymphoma
Fig. 3 (Siatkowski and associates). Standardized A-scan echograms of left optic nerve. Top, Primary gaze; arrows indicate optic nerve sheaths (6.3 mm). Bottom, Globe 30 degrees abducted; no change in nerve diameter (6.4 mm). venous occlusions, retinal vasculitis, and Horner's syndrome. 9 Spinal cord compression is the most common expression of central nerv ous system involvement in Hodgkin's disease and has been well documented. 1012 Intracranial involvement was described by Murchison 13 in 1870, and since then several other cases have been described. 11417 These cases document in volvement of the cerebral cortex, cerebellum, and various cranial nerves. Optic nerve infiltration occurs in various types of lymphoreticular malignancies, having been found in reticulum cell sarcoma, multiple myeloma, lymphomatoid granulomatosis, and
627
Fig. 4 (Siatkowski and associates). Top, Magnetic resonance imaging, axial view, fat-suppressed, shows marked gadolinium enhancement of left optic nerve (arrows). Bottom, Repeat scan six weeks after treatment. Note marked decrease in gadolinium en hancement of left optic nerve (arrows). eosinophilic granuloma. 18 The frequency of op tic nerve involvement in leukemia ranges from 2% to 33%.19·20 In non-Hodgkin's lymphomas, although central nervous system involvement occurs in up to 29% of cases, 21 optic neuropathy has been infrequently described.22'24 An early case of optic nerve involvement from Hodgkin's disease 2 manifested late in the disease and in the presence of widespread meningoencephalopathy with other clinical and laboratory abnormalities. Optic neuropathy as the initial manifestation of Hodgkin's disease is rare, but was described by Miller and Iliff,3 who found no other clinical abnormalities except for mild eosinophilia.
628
November, 1992
AMERICAN JOURNAL OF OPHTHALMOLOGY
Fig. 5 (Siatkowski and associates). Biopsy specimen of cervical lymph node shows diffuse lymphoid infil trate with a few eosinophils and polymorphonuclear cells; arrow indicates lacunar cell, a variant of ReedSternberg cell seen in nodular sclerosis Hodgkin's disease (hematoxylin and eosin, x 40). Litvak, Leder, and Kauvar 2 and Miller and Iliff8 showed that the optic neuropathy in Hodgkin's disease results from direct invasion of the nerve (and in their cases, the chiasm as well) by lymphoma cells, rather than from demyelination. Thus, radiotherapy is the treat ment of choice, with systemic corticosteroids having a secondary role. Coppeto, Monteiro, and Cannarozzi 25 described a secondary demyelinative optic neuritis from paranasal sinus lymphoma. The optic nerves appeared normal on computed tomography, and vision improved after treatment with intravenous corticoste roids, with no further recurrences. In over 95% of cases, central nervous system involvement in the lymphomas occurs with uncontrolled systemic relapse, 28 but optic neu ropathy as the sole manifestation of disease recurrence is rare. Kay24 described such a case in non-Hodgkin's lymphoma, but with many ma lignant cells in the cerebrospinal fluid, which indicated more diffuse lymphomatous meningi tis. In our case, the two main diagnostic consider ations were infiltrative optic neuropathy of lymphomatous origin; or a granulomatous or fungal infectious process, secondary to immunosuppression. Because systemic recurrence of Hodgkin's disease was not evident, the initial chemotherapy may have incompletely penetrat
ed the blood-brain barrier, with the optic neu ropathy resulting from residual cells in the central nervous system that escaped the origi nal chemotherapeutic course. The presence of axillary line paresthesias suggested lymphoma tous infiltration of thoracic méninges. Although investigation for recurrence of ma lignancy was noncontributory in our case, the solid thickening of the optic nerve, with no evidence of infection or cerebrospinal fluid ab normalities, most likely represented recurrence of lymphoma. Diagnostic optic nerve biopsy was briefly considered, but the rapid response to radiotherapy and the subsequent histologically documented disease recurrence confirmed the clinical impression of lymphomatous optic neuropathy. Our case is important from several stand points. First, optic neuropathy in Hodgkin's disease is not recognized as an initial sign of disease recurrence. Second, when infiltrative optic neuropathy occurs in the lymphoproliferative disorders, it is usually late in the disease course and is accompanied by other clinical signs and symptoms, as well as abnormal cere brospinal fluid and pathologic bone marrow. Third, our case demonstrates the value of standardized echography in the assessment of optic nerve diseases. In patients with a history of lymphoreticular malignancy and acute-onset optic neuropathy, magnetic resonance imaging and orbital echo graphy should be performed promptly. Solid thickening of the optic nerve echographically and marked gadolinium enhancement on neuroimaging indicates lymphomatous infiltration. The absence of other clinical and laboratory abnormalities, including the cerebrospinal flu id, are not inconsistent with this diagnosis, and prompt institution of radiotherapy and system ic corticosteroids may result in a rapid and dramatic improvement of visual function.
References 1. Ljungdahl, I., Strang, R., and Tovi, D.: Intracerebral Hodgkin's granuloma. Report of a case and review of the literature. Neurochirurgia 8:113, 1965. 2. Litvak, J., Leder, M. M., and Kauvar, A. J.: Case reports. Hodgkin's disease involving optic nerve and brain. J. Neurosurg. 21:798, 1964. 3. Miller, N. R., and Iliff, W. J.: Visual loss as the initial symptom in Hodgkin disease. Arch. Ophthalmol. 93:1158, 1975. 4. Christmas, N. J., Mead, M. D., Richardson,
Vol. 114, No. 5
Hodgkin's Lymphoma
E. P., and Albert, D. M.: Clinical pathological re view. Secondary optic nerve tumors. Surv. Ophthalmol. 36:196, 1991. 5. Schricker, J. L., and Smith, D. E.: Primary intracerebral Hodgkin's disease. Cancer 8:629, 1955. 6. Sparling, H. J., Jr., and Adams, R. D.: Primary Hodgkin's sarcoma of the brain. Arch. Pathol. 42:338, 1946. 7. Vogel, P. J., and Richland, K. J.: Involvement of the central nervous system by Hodgkin's disease. Case report with five year interval between primary spinal and cerebral lesions. Bull. L.A. Neurol. Soc. 20:83, 1955. 8. Gans, M. S., Byrne, S. F., and Glaser, J. S.: Standardized A-scan echography in optic nerve dis ease. Arch. Ophthalmol. 105:1232, 1987. 9. Walsh, F. B., and Hoyt, W. F.: Orbital, ocular, and intracranial tumors and related conditions. In Clinical Neuro-Ophthalmology, ed. 3. Baltimore, Williams & Wilkins, 1969, pp. 2300-2307. 10. Diamond, H. D.: Hodgkin's disease. Neurolog ic sequelae. Mo. Med. 54:945, 1957. 11. Hunt, W. E., Bouroncle, B. A., and Meagher, J. N.: Neurologic complications of leukemias and lymphomas. J. Neurosurg. 16:135, 1959. 12. Verda, D. J.: Malignant lymphomas of the spi nal epidural space. Surg. Clin. North Am. 24:1228, 1944. 13. Murchison, C : Case of "lymphadenoma" of the lymphatic system, spleen, liver, lungs, heart, diaphragm, dura mater, etc. Trans. Pathol. Soc. Lond. 21:372, 1870. 14. King, D. P., and Richardson, J. S.: Hodgkin's disease of the cerebellum. St. Thomas Hosp. Rep. 6:273, 1950. 15. Fein, S. B., and Nevill, V. A.: Cerebral Hodg kin's disease. Case report of Hodgkin's granuloma with cerebral invasion. Am. J. Med. 17:291, 1954.
629
16. Lascelles, R. G., and Burston, ].: Hodgkin's disease. Disease presenting with symptoms of crani al nerve involvement. Arch. Neurol. 7:359, 1962. 17. Kaufman, G.: Hodgkin's disease involving the central nervous system. Arch. Neurol. 13:555, 1968. 18. Kansu, T., Orr, L. S., Savino, P. J., Schatz, N. J., and Corbett, J. J.: Optic neuropathy as initial manifestation of lymphoreticular disease. A report of five cases. In Smith, J. L. (ed.): Neuro-ophthalmology Focus 1980. New York, Masson, 1979, pp. 125-136. 19. Allen, R. A., and Straatsma, B. R.: Ocular in volvement in leukemia and allied disorders. Arch. Ophthalmol. 66:490, 1961. 20. Leonardy, N. J., Rupani, M., Dent, G., and Klintworth, G. K.: Analysis of 135 autopsy eyes for ocular involvement in leukemia. Am. J. Ophthalmol. 109:436, 1990. 21. Bunn, P. A., Schein, P. S., Banks, P. M., and DeVita, V. T.: Central nervous system complications in patients with differentiated histiocytic and undifferentiated lymphoma. Leukemia revisited. Blood 47:3, 1976. 22. Kraus, A. M., and O'Rourke, J.: Lymphomatous optic neuritis. Arch. Ophthalmol. 70:173, 1963. 23. Bullock, J. D., Yares, B., Kelly, M., and McDonald, L.: Non-Hodgkin's lymphoma involving the optic nerve. Ann. Ophthalmol. 11:1477, 1979. 24. Kay, M. C : Optic neuropathy secondary to lymphoma. J. Clin. Neuro. Ophthalmol. 6:31, 1986. 25. Coppeto, J. R., Monteiro, M. L. R., and Cannarozzi, D. B.: Optic neuropathy associated with chronic lymphomatous meningitis. J. Clin. Neuro. Ophthalmol. 8:39, 1988. 26. Fetell, M. R.: Gliomas and lymphomas. In Rowland, L. P. (ed.): Merritt's Textbook of Neurolo gy, ed. 8. Philadelphia, Lea and Febiger, 1989, p. 307.
Hodgkin's disease is a rare cause of infiltrative optic neuropathy, which typically evolves late in the disease course. We managed an unusual case of isolated optic neuropathy in a 21-year-old man occurring during clinical remission from Hodgkin's disease. Radiotherapy and treatment with high-dose systemic corticosteroids resulted in dramatic improvement in vision. Even without other evidence of recurrent disease, acute-onset optic neuropathy in a patient with a history of a lymphoproliferative disorder should raise the question of a reemergence of the malignancy. C E N T R A L NERVOUS SYSTEM involvement in Hodgkin's disease may occur in up to 15% of cases, 1 but optic nerve infiltration is rare. Two histopathologically documented cases have been described. 2 · 3 More recently, a survey at the Massachusetts Eye and Ear Institute and the Massachusetts General Hospital identified without details only three cases over a 25-year period. 4 Hodgkin's disease of the central nervous sys tem may rarely be primary, 6 7 but usually is a result of hematogenous metastasis or direct tumor extension from contiguous structures, for example, the retroperitoneal space or paranasal sinuses. Optic neuropathy occurs typical ly late in the disease course, preceded by other central nervous system or systemic abnormali ties. Our case of infiltrative optic neuropathy in Hodgkin's disease documents that this compli cation may occur as the sole manifestation of disease recurrence in a patient otherwise in clinical remission.
Accepted for publication Aug. 14, 1992. From the Bascom Palmer Eye Institute, Miami, Florida. This study was presented in part at the 24th Annual Frank B. Walsh Meeting, Los Angeles, California, Feb. 28, 1992. Reprint requests to Joel S. Glaser, M.D., 900 N.W. 17th St., Miami, FL 33136.
Case Report A 21-year-old man was initially examined in October 1988 because of complaints of fever, and neck and inguinal masses. Pathologic diag nosis was nodular sclerosis Hodgkin's disease, stage HIB (disease above and below the dia phragm, and systemic symptoms). Twelve cy cles of chemotherapy were prescribed for the patient, but he received only five because of adverse effects (one course of methotrexate, vincristine sulfate, procarbazine, and prednisone; three courses of doxorubicin hydrochloride, bleomycin, vincristine, and dacarbazine; and one course of bleomycin, vincristine, cyclophosphamide, procarbazine, and prednisone). No chemotherapy was received after May 1989 and the patient remained without symptoms for more than two years. On Aug. 11, 1991, the patient was examined at our institution for loss of vision in the left eye two weeks previously, which was associated with severe orbital pain made worse with ocu lar movement. The patient also complained of a mild frontal headache and bilateral paresthesias of the chest that extended down both ante rior axillary lines. Neuro-ophthalmic examination disclosed a visual acuity of 20/20 in the right eye, with a full visual field, and normal anterior segment and fundus. The visual acuity in the left eye was counting fingers, with a large central scotoma and an afferent pupillary defect that measured 3.0 log units. The anterior segment was normal and there was no vitreitis. The left optic disk was diffusely swollen with surrounding hemor rhages (Fig. 1). Ocular motility was normal. B-scan echography showed a normal right optic nerve and a notably enlarged left optic nerve with marked disk elevation (Fig. 2). By standardized A-scan echography, the right op tic nerve measured 3.8 mm with a positive 30-degree test (3.2 mm), which indicated increased subarachnoid fluid around the nerve. 8 The left optic nerve was markedly en-
©AMERICAN JOURNAL OF OPHTHALMOLOGY 114:625-629, NOVEMBER, 1992
625
626
November, 1992
AMERICAN JOURNAL OF OPHTHALMOLOGY
Fig. 1 (Siatkowski and associates). Swollen left optic disk, and peripapillary retinal folds and hemor rhages. larged with low reflectivity. Its diameter was 6.3 mm with a negative 30-degree test (6.4 mm), which suggested solid thickening of the nerve (Fig. 3). (Normal A-scan values of optic nerve diameter range from 2.3 to 3.3 mm. 8 ) Magnetic resonance imaging demonstrated en largement and gadolinium enhancement of the left optic nerve from the globe to the optic canal (Fig. 4). The right optic nerve was normal. Results of a general physical examination were normal, without adenopathy or visceromegaly. Lumbar puncture disclosed an opening pressure of 200 mm H 2 0, a protein concentra tion of 40 mg/dl, a glucose level of 65 m g / d l , and no cells. Cerebrospinal fluid VDRL, cryptococcal antigen, and bacterial and fungal cul tures were negative. Cytology screen, including immunoassay, detected no malignant cells. Fur ther examination included thoracic radiogra phy, computed tomography of the abdomen arid pelvis, and bone marrow biopsy, all of which had normal results. Lymphomatous infiltration of the left optic nerve was strongly suspected, and 2,000 cGy of radiation were delivered over ten daily sessions to the left optic nerve. Intravenous methylprednisolone, 250 mg four times daily, was adminis tered simultaneously for three days, followed by oral prednisone, 60 mg daily, which was tapered over a three-week period. Within one week, the visual acuity in the left
Fig. 2 (Siatkowski and associates). B-scan echograms of left optic nerve. Top, Vertical cross section; arrows indicate enlarged nerve sheath. Bottom, Lon gitudinal section through elevated disk and anterior optic nerve (ON). eye improved to 20/400, with a decrease in the size of the scotoma. A six-week follow-up ex amination on Sept. 25, 1991, disclosed a visual acuity of 20/60 in the left eye. The disk swell ing had resolved, but with a trace of temporal pallor. The left afferent pupillary defect now measured 0.9 log unit. Repeat magnetic reso nance imaging six weeks after treatment showed a left optic nerve of normal size with only minimal gadolinium enhancement (Fig. 4). Eight weeks after the visual symptoms devel oped, a 1.5-cm right anterior cervical lymph node appeared. A biopsy confirmed nodular sclerosis Hodgkin's disease (Fig. 5), and chem otherapy was reinstituted.
Discussion Hodgkin's disease causes a variety of oph thalmic problems, including oculomotor pal sies, proptosis, iritis, retinal arterial and
Vol. 114, No. 5
Hodgkin's Lymphoma
Fig. 3 (Siatkowski and associates). Standardized A-scan echograms of left optic nerve. Top, Primary gaze; arrows indicate optic nerve sheaths (6.3 mm). Bottom, Globe 30 degrees abducted; no change in nerve diameter (6.4 mm). venous occlusions, retinal vasculitis, and Horner's syndrome. 9 Spinal cord compression is the most common expression of central nerv ous system involvement in Hodgkin's disease and has been well documented. 1012 Intracranial involvement was described by Murchison 13 in 1870, and since then several other cases have been described. 11417 These cases document in volvement of the cerebral cortex, cerebellum, and various cranial nerves. Optic nerve infiltration occurs in various types of lymphoreticular malignancies, having been found in reticulum cell sarcoma, multiple myeloma, lymphomatoid granulomatosis, and
627
Fig. 4 (Siatkowski and associates). Top, Magnetic resonance imaging, axial view, fat-suppressed, shows marked gadolinium enhancement of left optic nerve (arrows). Bottom, Repeat scan six weeks after treatment. Note marked decrease in gadolinium en hancement of left optic nerve (arrows). eosinophilic granuloma. 18 The frequency of op tic nerve involvement in leukemia ranges from 2% to 33%.19·20 In non-Hodgkin's lymphomas, although central nervous system involvement occurs in up to 29% of cases, 21 optic neuropathy has been infrequently described.22'24 An early case of optic nerve involvement from Hodgkin's disease 2 manifested late in the disease and in the presence of widespread meningoencephalopathy with other clinical and laboratory abnormalities. Optic neuropathy as the initial manifestation of Hodgkin's disease is rare, but was described by Miller and Iliff,3 who found no other clinical abnormalities except for mild eosinophilia.
628
November, 1992
AMERICAN JOURNAL OF OPHTHALMOLOGY
Fig. 5 (Siatkowski and associates). Biopsy specimen of cervical lymph node shows diffuse lymphoid infil trate with a few eosinophils and polymorphonuclear cells; arrow indicates lacunar cell, a variant of ReedSternberg cell seen in nodular sclerosis Hodgkin's disease (hematoxylin and eosin, x 40). Litvak, Leder, and Kauvar 2 and Miller and Iliff8 showed that the optic neuropathy in Hodgkin's disease results from direct invasion of the nerve (and in their cases, the chiasm as well) by lymphoma cells, rather than from demyelination. Thus, radiotherapy is the treat ment of choice, with systemic corticosteroids having a secondary role. Coppeto, Monteiro, and Cannarozzi 25 described a secondary demyelinative optic neuritis from paranasal sinus lymphoma. The optic nerves appeared normal on computed tomography, and vision improved after treatment with intravenous corticoste roids, with no further recurrences. In over 95% of cases, central nervous system involvement in the lymphomas occurs with uncontrolled systemic relapse, 28 but optic neu ropathy as the sole manifestation of disease recurrence is rare. Kay24 described such a case in non-Hodgkin's lymphoma, but with many ma lignant cells in the cerebrospinal fluid, which indicated more diffuse lymphomatous meningi tis. In our case, the two main diagnostic consider ations were infiltrative optic neuropathy of lymphomatous origin; or a granulomatous or fungal infectious process, secondary to immunosuppression. Because systemic recurrence of Hodgkin's disease was not evident, the initial chemotherapy may have incompletely penetrat
ed the blood-brain barrier, with the optic neu ropathy resulting from residual cells in the central nervous system that escaped the origi nal chemotherapeutic course. The presence of axillary line paresthesias suggested lymphoma tous infiltration of thoracic méninges. Although investigation for recurrence of ma lignancy was noncontributory in our case, the solid thickening of the optic nerve, with no evidence of infection or cerebrospinal fluid ab normalities, most likely represented recurrence of lymphoma. Diagnostic optic nerve biopsy was briefly considered, but the rapid response to radiotherapy and the subsequent histologically documented disease recurrence confirmed the clinical impression of lymphomatous optic neuropathy. Our case is important from several stand points. First, optic neuropathy in Hodgkin's disease is not recognized as an initial sign of disease recurrence. Second, when infiltrative optic neuropathy occurs in the lymphoproliferative disorders, it is usually late in the disease course and is accompanied by other clinical signs and symptoms, as well as abnormal cere brospinal fluid and pathologic bone marrow. Third, our case demonstrates the value of standardized echography in the assessment of optic nerve diseases. In patients with a history of lymphoreticular malignancy and acute-onset optic neuropathy, magnetic resonance imaging and orbital echo graphy should be performed promptly. Solid thickening of the optic nerve echographically and marked gadolinium enhancement on neuroimaging indicates lymphomatous infiltration. The absence of other clinical and laboratory abnormalities, including the cerebrospinal flu id, are not inconsistent with this diagnosis, and prompt institution of radiotherapy and system ic corticosteroids may result in a rapid and dramatic improvement of visual function.
References 1. Ljungdahl, I., Strang, R., and Tovi, D.: Intracerebral Hodgkin's granuloma. Report of a case and review of the literature. Neurochirurgia 8:113, 1965. 2. Litvak, J., Leder, M. M., and Kauvar, A. J.: Case reports. Hodgkin's disease involving optic nerve and brain. J. Neurosurg. 21:798, 1964. 3. Miller, N. R., and Iliff, W. J.: Visual loss as the initial symptom in Hodgkin disease. Arch. Ophthalmol. 93:1158, 1975. 4. Christmas, N. J., Mead, M. D., Richardson,
Vol. 114, No. 5
Hodgkin's Lymphoma
E. P., and Albert, D. M.: Clinical pathological re view. Secondary optic nerve tumors. Surv. Ophthalmol. 36:196, 1991. 5. Schricker, J. L., and Smith, D. E.: Primary intracerebral Hodgkin's disease. Cancer 8:629, 1955. 6. Sparling, H. J., Jr., and Adams, R. D.: Primary Hodgkin's sarcoma of the brain. Arch. Pathol. 42:338, 1946. 7. Vogel, P. J., and Richland, K. J.: Involvement of the central nervous system by Hodgkin's disease. Case report with five year interval between primary spinal and cerebral lesions. Bull. L.A. Neurol. Soc. 20:83, 1955. 8. Gans, M. S., Byrne, S. F., and Glaser, J. S.: Standardized A-scan echography in optic nerve dis ease. Arch. Ophthalmol. 105:1232, 1987. 9. Walsh, F. B., and Hoyt, W. F.: Orbital, ocular, and intracranial tumors and related conditions. In Clinical Neuro-Ophthalmology, ed. 3. Baltimore, Williams & Wilkins, 1969, pp. 2300-2307. 10. Diamond, H. D.: Hodgkin's disease. Neurolog ic sequelae. Mo. Med. 54:945, 1957. 11. Hunt, W. E., Bouroncle, B. A., and Meagher, J. N.: Neurologic complications of leukemias and lymphomas. J. Neurosurg. 16:135, 1959. 12. Verda, D. J.: Malignant lymphomas of the spi nal epidural space. Surg. Clin. North Am. 24:1228, 1944. 13. Murchison, C : Case of "lymphadenoma" of the lymphatic system, spleen, liver, lungs, heart, diaphragm, dura mater, etc. Trans. Pathol. Soc. Lond. 21:372, 1870. 14. King, D. P., and Richardson, J. S.: Hodgkin's disease of the cerebellum. St. Thomas Hosp. Rep. 6:273, 1950. 15. Fein, S. B., and Nevill, V. A.: Cerebral Hodg kin's disease. Case report of Hodgkin's granuloma with cerebral invasion. Am. J. Med. 17:291, 1954.
629
16. Lascelles, R. G., and Burston, ].: Hodgkin's disease. Disease presenting with symptoms of crani al nerve involvement. Arch. Neurol. 7:359, 1962. 17. Kaufman, G.: Hodgkin's disease involving the central nervous system. Arch. Neurol. 13:555, 1968. 18. Kansu, T., Orr, L. S., Savino, P. J., Schatz, N. J., and Corbett, J. J.: Optic neuropathy as initial manifestation of lymphoreticular disease. A report of five cases. In Smith, J. L. (ed.): Neuro-ophthalmology Focus 1980. New York, Masson, 1979, pp. 125-136. 19. Allen, R. A., and Straatsma, B. R.: Ocular in volvement in leukemia and allied disorders. Arch. Ophthalmol. 66:490, 1961. 20. Leonardy, N. J., Rupani, M., Dent, G., and Klintworth, G. K.: Analysis of 135 autopsy eyes for ocular involvement in leukemia. Am. J. Ophthalmol. 109:436, 1990. 21. Bunn, P. A., Schein, P. S., Banks, P. M., and DeVita, V. T.: Central nervous system complications in patients with differentiated histiocytic and undifferentiated lymphoma. Leukemia revisited. Blood 47:3, 1976. 22. Kraus, A. M., and O'Rourke, J.: Lymphomatous optic neuritis. Arch. Ophthalmol. 70:173, 1963. 23. Bullock, J. D., Yares, B., Kelly, M., and McDonald, L.: Non-Hodgkin's lymphoma involving the optic nerve. Ann. Ophthalmol. 11:1477, 1979. 24. Kay, M. C : Optic neuropathy secondary to lymphoma. J. Clin. Neuro. Ophthalmol. 6:31, 1986. 25. Coppeto, J. R., Monteiro, M. L. R., and Cannarozzi, D. B.: Optic neuropathy associated with chronic lymphomatous meningitis. J. Clin. Neuro. Ophthalmol. 8:39, 1988. 26. Fetell, M. R.: Gliomas and lymphomas. In Rowland, L. P. (ed.): Merritt's Textbook of Neurolo gy, ed. 8. Philadelphia, Lea and Febiger, 1989, p. 307.
